The prevalence of overweight and obesity among adolescents with Down syndrome exceeds 50% and is significantly greater than rates observed in the general population. This condition persists into adulthood and contributes to the development of additional secondary health conditions. Thus, obesity represents a predominant source of health disparity. It remains unclear what causes the higher prevalence of obesity among adolescents with Down syndrome. Glucocorticoid (i.e. cortisol) function may be a novel neuroendocrine mechanism to explain the increased risk of obesity in this population. Recent research suggests that young adults with Down syndrome exhibit cortisol dysregulation compared to adults without disabilities. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and cortisol function have been shown to promote weight gain and greater abdominal fat mass in the general population. However, it remains unclear whether differences in cortisol functioning in adolescents with Down syndrome contribute to the greater prevalence of obesity. Furthermore, many interventions to address pediatric obesity involve exercise. Normal cortisol response to exercise is expected to have a protective effect on obesity development, but it is unclear how cortisol response to exercise is associated with obesity in adolescents with Down syndrome. This fellowship application, therefore proposes to study how cortisol function mediates the association between fat mass (obesity) and Down syndrome under two conditions: 1) daily living in the natural environment; and 2) in response to a bout of moderate-intensity exercise. Pediatric obesity is significant public health problem, especially in populations with pediatric disabilities. This research will examine a novel mechanism to explain the greater obesity prevalence among youth with Down syndrome. Through studying this mechanism during daily life and in the context of a modifiable health behavior, this proposed study may promote the development of effective interventions and prevention programs in the future. This F31 Pre-doctoral Fellowship seeks to expand my current doctoral training and research potential. The primary goal will be to gain research skills that will enable me to study neuroendocrine and physiological factors that contribute to health disparities and obesity among youth with Down syndrome. The award will provide: 1) more time to focus on the proposed research project; and 2) additional resources to increase my research training in advanced exercise physiology, metabolic endocrinology and the pathophysiology of obesity. The comprehensive training plan and proposed research project will examine a novel mechanism that could better explain obesity in this at-risk population. Training will provide me with a rane of research tools to study obesity in populations with pediatric disabilities and develop innovative future interventions to reduce pediatric obesity throughout my career.